Diseases such as bronchial asthma and pulmonary hypertension may involve changes in the contractile state of smooth muscle in intrapulmonary vessels and airways. However, effective treatment of these diseases requires fundamental knowledge concerning morphology, physiology and pharmacology of the airways and vessels. The objective of the proposed research is to improve our knowledge of the regulation of intrapulmonary vessels and airways by hormonal factors such as prostaglandins, peptides and vasoactive amines. In order to accomplish this objective, helical segments of large and small airways and of intrapulmonary artery and vein will be removed from the lungs of several laboratory species. The helical segments will be mounted in an isolated organ bath in which temperature, pH, pO2, PCO2 and resting load can be carefully controlled and changes in isometric force generation recorded on a polygraph. The effects of prostaglandins, endoperoxides, prostacyclins, and thromboxanes on isometric force output will be studied in intrapulmonary vessels and airways. Furthermore, the effects of a number of vasoactive hormones and drugs which may be useful in treating pulmonary hypertension and bronchial asthma will be assessed. In addition, studies will be undertaken to identify the pools of calcium utilized for prostaglandin induced contraction. The final objectives of the proposal are to investigate calcium metabolism by subcellular organelles and correlate changes in bronchomotor activity with contractility changes in airway smooth muscle.